A Study to Learn How BAY94-8862 Moves Into, Through and Out of the Body, How Safe it is and How it Affects the Body in Adult Participants With Reduced Kidney Function and in Healthy Participants With Similar Age, Weight and Gender Distribution

Chronic Kidney Disease Clinical Trial

Official title:

Investigation of Pharmacokinetics, Safety, and Tolerability of BAY 94-8862 in Male and Female Subjects With Renal Impairment and in Age- and Weight-matched Healthy Subjects Following a Single Oral Dose of 10 mg BAY 94-8862 IR Tablet in a Single-center, Non-randomized, Non-controlled, Non-blinded, Observational Study With Group Stratification

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04908436
• Other study ID #: 14509
• Secondary ID: 2010-022321-16
• Status: Completed
• Phase: Phase 1
• Start date: October 27, 2010
• Est. completion date: January 27, 2012

Study information

• Verified date: January 2022
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Researchers are looking for a better way to treat people who have worsening of chronic heart failure, a long-term condition where the heart does not pump blood as well as it should.

In this study researchers wanted to learn more about a new substance called finerenone (BAY94-8862).

Finerenone is a substance that blocks the activation of a protein in the body called mineralocorticoid receptor (MR). An increased activation of MR is involved in the development of hypertension, organ damage and worsening of heart failure. Many patients with worsening chronic heart failure also suffer from chronic kidney disease. Chronic kidney disease is a long-term decrease in the kidneys' ability to work properly.

The researchers studied how finerenone moves into, through and out of the body. The researchers also looked at how safe finerenone is and how it affects the body. The main purpose of this study was to help researchers develop recommendations for the amount of the substance (the dosing) to be given to patients with reduced kidney function.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: January 27, 2012
• Est. primary completion date: May 5, 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria:

• The informed consent must be signed before any study specific tests or procedures are done;

• Male participants and female participants without childbearing potential (postmenopausal women with 12 month of spontaneous amenorrhea or with 6 month of spontaneous amenorrhea and serum follicle-stimulating hormone (FSH) levels >30 mIU/mL; women with 6 weeks post bilateral ovarectomy, women with bilateral tubal ligation, and women with hysterectomy);

• Age: 18 to 79 years at the first screening examination;

• Race: White;

• Body mass index (BMI): = 18 and = 34 kg / m2;

Participants with renal impairment

• Creatinine clearance (CLCR) = 80 mL/min determined from a 24 hour urine collection interval 2 - 14 days prior to dosing;

• Stable renal disease, ie a serum creatinine value determined at least 3-6 months before the pre-study visit should not vary by more than 20% from the serum creatinine value determined at the pre-study visit;

Healthy participants

• Mean age and body weight in Group 1 (control group, healthy participants) and Groups 2 - 4 should not vary by more than +/- 10 years and +/- 10 kg, respectively.

Exclusion Criteria:

• Participation in another clinical trial during the preceding 3 months for multiple dose studies and 1 month for single-dose studies; (final examination from previous study to first treatment of new study);

• Exclusion periods from other studies or simultaneous participation in other clinical studies;

• Donation of more than 100 mL of blood within 4 weeks before the first study drug administration or more than 500 mL in the preceding 3 months;

• Regular use of following medication during or within the 1 - 2 weeks preceding the study:

• concomitant administration of other Aldosterone-antagonists (eg. eplerenone or spironolactone), potassium-sparing diuretics, potassium supplements, nonsteroidal anti-inflammatory drugs like ASS (secondary prevention with a dose of 100 mg daily is allowed), indomethacin or ibuprofen

• concomitant use of cytochrome P450 isoenzyme 3A4 (CYP3A4) inducers (eg St. John´s wort, rifampicin, carbamazepin, phenytoin, phenobarbital, bosentan)

• concomitant use of weak to moderate CYP3A4 inhibitors (eg erythromycin, quinupristin/dalfopristin, saquinavir, fluconazole, amiodarone, diltiazem, fluvoxamine, verapamil, valproic acid, fluoxetine, grapefruit juice)

• strong inhibitors of CYP3A4 (eg human immunodeficiency virus (HIV) protease inhibitors like indinavir, nelfinavir, ritonavir, atazanavir, lopinavir, amprenavir and saquinavir; macrolide/ketolide antibiotics like clarithromycin, telithromycin; antimycotic agents like itraconazole and ketoconazole [topical formulations will be allowed]; nefazodone)

• moderate and strong inhibitors of cytochrome P450 isoenzyme 2C8 (CYP2C8) (eg gemfibrozil, montelukast, trimethoprim, glitazones)

• Women of childbearing potential, pregnant or lactating women;

• Positive results for hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), human immune deficiency virus antibodies (anti-HIV 1+2);

• Serum potassium level = 5.5 mmol/L;

• Serum sodium level = 130 mmol/L;

For participants with renal impairment

• Acute renal failure;

• Acute nephritis;

• Any organ transplant;

• Failure of any other major organ system other than the kidney;

• Diastolic blood pressure (DBP) > 100 mmHg and/or systolic blood pressure (SBP) > 180 mmHg (at the pre-study examination; readings taken at the end of the dosing interval of antihypertensive medication, if any);

• Heart rate below 45 or above 110 BPM at screening visit;

• Hemoglobin < 8 g/dL;

• Serum albumin < 30 g/L;

• Severe cerebrovascular or cardiac disorders, eg myocardial infarction less than 6 months prior to dosing, congestive heart failure of New York Heart Association (NYHA) grade III or IV, decompensated heart failure, severe arrhythmia requiring antiarrhythmic treatment;

For healthy participants

• A history of relevant diseases of vital organs, of the central nervous system or other organs;

• Systolic blood pressure below 100 mmHg or above 145 mmHg;

• Diastolic blood pressure above 95 mmHg;

• Heart rate below 45 or above 95 BPM at screening visit;

• Clinically relevant deviations of the screened laboratory parameters in clinical chemistry, hematology, or urinalysis from reference range;

• Relevant deviation from the normal range in the clinical examination as judged by the investigator.

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Finerenone (BAY94-8862)
10 mg BAY94-8862 immediate release (IR) tablet, administered orally

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Heinig R, Kimmeskamp-Kirschbaum N, Halabi A, Lentini S. Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone (BAY 94-8862) in Individuals With Renal Impairment. Clin Pharmacol Drug Dev. 2016 Nov;5(6):488-501. doi: 10 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration vs time curve from zero to infinity for total (bound and unbound) drug after single dose administration of BAY94-8862 (AUC)	AUC for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Primary	Maximum total (bound and unbound) drug concentration in plasma after single dose administration of BAY94-8862 (Cmax)	Cmax for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Primary	AUC for unbound drug (AUCu)	AUCu for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Primary	Cmax for unbound drug (Cmax,u)	Cmax,u BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Primary	AUC divided by dose per kg body weight (AUCnorm)	AUCnorm for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Primary	AUCnorm for unbound drug (AUCu,norm)	AUCu, norm for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Primary	Cmax divided by dose per body weight (Cmax,norm)	Cmax, norm for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Primary	Cmax,norm for unbound drug (Cmax,u,norm)	Cmax,u,norm for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Secondary	Plasma renin activity (PRA)	Change from baseline in plasma renin activity	Prior to dosing and 12 hours post-dose
Secondary	Plasma angiotensin II	Change from baseline in plasma angiotensin II	Prior to dosing and 12 hours post-dose
Secondary	Serum aldosterone	Change from baseline in serum aldosterone	Prior to dosing and 12 hours post-dose
Secondary	Plasminogen activator inhibitor-1 (PAI-1)	Change from baseline in PAI-1	Prior to dosing and 12 hours post-dose
Secondary	Urinary volume	Change in volume of urine excreted	Prior to dosing up to 24 hours post-dose
Secondary	Urinary creatinine	Change in urine creatinine concentrations	Prior to dosing up to 24 hours post-dose
Secondary	Urinary electrolytes	Change in urinary electrolytes	Prior to dosing up to 24 hours post-dose
Secondary	Half-life associated with the terminal slope (t½)	t½ for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Secondary	Fraction unbound (fu)	fu for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	1 hour and 6 hours post-dose
Secondary	AUC divided by dose (AUC/D)	AUC/D for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Secondary	AUC from time 0 to the last data point (AUC(0-tlast))	AUC(0-tlast) for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Secondary	Cmax divided by dose (Cmax/D)	Cmax/D for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Secondary	Time to reach Cmax (tmax)	Time to reach Cmax (in case of two identical Cmax values, the first tmax was to be used) for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Secondary	Mean residence time (MRT)	MRT for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Secondary	Total body clearance of drug calculated after extravascular administration (CL/F)	CL/F for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Secondary	Total body clearance of unbound drug from plasma calculated after oral administration (apparent oral unbound clearance) (CLu/F)	CLu/F for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Secondary	Apparent volume of distribution during terminal phase after extravascular administration (Vz/F)	Vz/F for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Secondary	Amount excreted into urine from 0 to 96 h (end of urine sampling) after study drug administration (AE,ur)	AE,ur for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Secondary	Percent amount excreted into urine from 0 to 96 h (end of urine sampling) after study drug administration (%AE,ur)	%AE,ur for BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Secondary	Renal body clearance of drug (CLR)	CLR of BAY94-8862 and its metabolites M1 (BAY1040818), M2 (BAY1088089) and M3 (BAY1088090)	Up to 96 hours post-dose
Secondary	Number of participants with adverse events		Approximately 5 weeks

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